Cancer gene therapy · 2025
MALNC: a new mutant NPM1/IDH2R140 and PML-RARA-associated lncRNA with impact on AML cell proliferation, maturation and drug response.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Cozzi Elisabetta, Neddermeyer Anne, Zhong Xiangfu, Gamboa-Cedeño Angelica María, Kanellis Dimitris C, Österroos Albin, Björklund My, Struyf Nona, Karlsson Kasper, Qu Ying, Månsson Alma, Pandzic Tatjana, Bengtzén Sofia, Nilsson Christer, Fiskesund Roland, Baliakas Panagiotis, Erkers Tom, Bartek Jiri, Kallioniemi Olli-Pekka, Qian Hong, Lennartsson Andreas, Lehmann Sören
Аннотация
As the non-coding genome remains poorly characterized in acute myeloid leukemia (AML), we aimed to identify and functionally characterize novel long non-coding RNAs (lncRNAs) relevant to AML biology and treatment. We first identified lncRNAs overexpressed in AML blasts and, among them, discovered a novel transcript, which we named myeloid and AML-associated intergenic long non-coding RNA (MALNC). MALNC is overexpressed in AML, particularly in cases with the PML-RARA fusion or IDH2R140/NPM1 co-mutations, and is associated with a distinct gene expression profile. Functional studies showed that MALNC knockout impairs AML cell proliferation and colony formation, enhances ATRA-induced differentiation, and sensitizes cells to arsenic trioxide. Transcriptomic analysis revealed that MALNC loss alters the expression of retinoic acid pathway genes, and chromatin binding studies showed that MALNC binds to genes related to the retinoic acid and Rho GTPase pathways. In conclusion, we have identified MALNC as a novel lncRNA that promotes leukemic cell proliferation, counteracts ATRA-induced differentiation, and modulates drug sensitivity in AML.